p-Toluenesulfonic acid monohydrate → HCID 73297205, compound

HRID 592413Notes

Reaction equation

HRID 592413 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[F:23][CH:24]([F:31])[N:25]1[CH:29]=[C:28]([NH2:30])[CH:27]=[N:26]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)=[N:7][C:2]([NH:30][C:28]2[CH:27]=[N:26][N:25]([CH:24]([F:31])[F:23])[CH:29]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 33781814HCID 33781814, compoundHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 73297205HCID 73297205, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.076 g, 0.225 mmol), 1-(difluoromethyl)-1H-pyrazol-4-amine A28 (0.030 g, 0.23 mmol) and p-toluenesulfonic acid monohydrate (0.004 g, 0.023 mmol) in 1,4-dioxane (4.0 mL) was stirred in a microwave reactor at 120° C. for 2 hours. The volatiles were evaporated in vacuo and the residue was purified by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-5% MeOH in DCM). Fractions containing suspected product were combined and the solvent removed in vacuo to give a residue that was purified further by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-60% EtOAc in petroleum benzine 40-60° C.). Fractions containing suspected product were combined, the solvent was removed in vacuo and the resulting solid purified by prep-LCMS to give the title compound 34 as a white solid (0.005 g, 5%). LCMS-B: rt 3.41 min; m/z 433 [M+H]+.

Workup

  1. customThe volatiles were evaporated in vacuo
  2. customthe residue was purified by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-5% MeOH in DCM)
  3. additionFractions containing suspected product
  4. customthe solvent removed in vacuo
  5. customto give a residue that
  6. customwas purified further by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-60% EtOAc in petroleum benzine 40-60° C.)
  7. additionFractions containing suspected product
  8. customthe solvent was removed in vacuo
  9. customthe resulting solid purified by prep-LCMS

Sources & evidence

ORD record
ord-7b9254f5eece4c21b8f7d7931186e7db
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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